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Comprehensive interrogation of natural TALE DNA-binding modules and transcriptional repressor domains
Open accessAbstract
Transcription activator-like effectors are sequence-specific DNA-binding proteins that harbour modular, repetitive DNA-binding domains. Transcription activator-like effectors have enabled the creation of customizable designer transcriptional factors and sequence-specific nucleases for genome engineering. Here we report two improvements of the transcription activator-like effector toolbox for achieving efficient activation and repression of endogenous gene expression in mammalian cells. We show that the naturally occurring repeat-variable diresidue Asn-His (NH) has high biological activity and specificity for guanine, a highly prevalent base in mammalian genomes. We also report an effective transcription activator-like effector transcriptional repressor architecture for targeted inhibition of transcription in mammalian cells. These findings will improve the precision and effectiveness of genome engineering that can be achieved using transcription activator-like effectors. The peptide sequence of transcription activator-like effectors (TALEs) can be customized to tailor the binding of TALEs to specific DNA sequences. Conget al. improve TALE specificity for guanine binding and use a genetic construct based on TALEs to efficiently repress expression of a target gene.
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TAL effectors: customizable proteins for DNA targeting
Bogdanove, A. J., & Voytas, D. F. (2011) · Science · doi:10.1126/science.1204094 · Cited by 984
Cited by
CRISPR-Mediated Modular RNA-Guided Regulation of Transcription in Eukaryotes
Gilbert, L. A., Larson, M. H., Morsut, L., Liu, Z., Brar, G. A., Torres, S. E., Stern-Ginossar, N., Brandman, O., Whitehead, E. H., Doudna, J. A., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.044 · Cited by 3,696
“the TALE proteins, have been fused to transcription activators and repressors to modulate gene expression (Cong et al., 2012; Deuschle et al., 1995; Gossen andBujard, 1992; Hathaway et al., 2012; Maeder et al., 2013; Margolin et al., 1994; PerezPinera et al., 2013; Sadowski et al., 1988; Zhang et al., 2000).”
BackgroundTALENs: A widely applicable technology for targeted genome editing
Joung, J. K., & Sander, J. D. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3486 · Cited by 1,650
“…that TALE-based activators and repressors can be used to modulate expression of endogenous genes in plants and human cells, with changes in gene or protein expression in the range of two-to 30-fold, 15, 19, 29, 93–98 but the vast majority of these proteins show relatively modest levels of activity.”
Bikard, D., Jiang, W., Samai, P., Hochschild, A., Zhang, F., & Marraffini, L. A. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt520 · Cited by 1,145
Self-citationThakore, P. I., D'Ippolito, A. M., Song, L., Safi, A., Shivakumar, N. K., Kabadi, A. M., Reddy, T. E., Crawford, G. E., & Gersbach, C. A. (2015) · Nature Methods · doi:10.1038/nmeth.3630 · Cited by 1,012
Optical control of mammalian endogenous transcription and epigenetic states
Konermann, S., Brigham, M. D., Trevino, A. E., Hsu, P. D., Heidenreich, M., Cong, L., Platt, R. J., Scott, D. A., Church, G. M., & Zhang, F. (2013) · Nature · doi:10.1038/nature12466 · Cited by 803
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Metadata
- Authors
- Cong, L., Zhou, R., Kuo, Y.-C., Cunniff, M., & Zhang, F.
- Venue
- Nature Communications
- Published
- 2012-07-24
- Volume
- 3
- Issue
- 1
- Pages
- 968-968
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2158023793
- Cited by
- 337
- References
- 1
- FWCI
- 20.10
- Type
- journal article
- Language
- en
- Open access
- bronze
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